Tetrahydro-4-quinolinamines identified as novel P2Y(1) receptor antagonists.
High-throughput screening of the GSK compound collection against the P2Y(1) receptor identified a novel series of tetrahydro-4-quinolinamine antagonists. Optimal substitution around the piperidine group was pivotal for ensuring activity. An exemplar analog from this series was shown to inhibit platelet aggregation.
Morales-Ramos
Angel I
AI
Department of Chemistry, Metabolic Pathways Centre for Excellence in Drug Discovery, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA. joseph.p.marino@gsk.com
Mecom
John S
JS
Kiesow
Terry J
TJ
Graybill
Todd L
TL
Brown
Gregory D
GD
Aiyar
Nambi V
NV
Davenport
Elizabeth A
EA
Kallal
Lorena A
LA
Knapp-Reed
Beth A
BA
Li
Peng
P
Londregan
Allyn T
AT
Morrow
Dwight M
DM
Senadhi
Shobha
S
Thalji
Reema K
RK
Zhao
Steve
S
Burns-Kurtis
Cynthia L
CL
Marino
Joseph P
JP
D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D015394:Molecular Structure; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000188:drug therapy
C534104:1,2,3,4-tetrahydro-4-quinolinamine; D000634:Aminoquinolines; C546382:P2RY1 protein, human; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1